ROLE OF CORONARY PRESSURE & FFR IN MULTIVESSEL DISEASE

ROLE OF CORONARY PRESSURE & FFR IN MULTIVESSEL DISEASE Angioplasty Summit TCT ASIA Seoul, Korea, april 24th, 2008 Nico H. J. Pijls, MD, PhD Catharina Hospital, Eindhoven, The Netherlands

A rather common patient in our cath lab today. 72-year-old male, stable angina class 3 small non-stemi 3 weeks earlier, no diagnostic -ECG residual angina class 2-3 positive exercise stress test Coronary angiography

FAME STUDY patient # 1249 June 25th, 2007 LCA

FAME STUDY patient # 1249 June 25th, 2007 RCA

A rather common patient in our cath lab today. 72-year-old male, stable angina class 3 small non-stemi 3 weeks earlier, no diagnostic -ECG residual angina class 2-3 positive exercise stress test Coronary angiography - 50% LAD artery - 50% lntermediate branch - 90% LCX artery - 70 % RCA proximal - 50% RCA mid

A rather common patient in our cath lab today. BUT HOW TO PROCEED..??? It is not the question IF stenting is indicated, but WHERE and HOW MANY

Several scenario s If you are a very practical dedicated interventionalist: - stent the LCX and see what happens afterwards If you are a more agressive interventionalist and believe that every lesion should be treated: - nice lesions to fix, let s place 3 or 4 stents (expensive, maybe unnecessary or even increasing risk, but neither the doctor, nor the patient will ever know) If you are strictly following guidelines ( and not too familiar with FFR) : - let s do a MIBI-SPECT first (expensive, time consuming, not very practical)

Which lesions should be stented? IMPORTANT ISSUE TO KEEP IN MIND In patients with coronary artery disease, the most important factor with respect to both functional class (symptoms) and prognosis (outcome) Is the presence and extent of inducible ischemia

EVIDENCE-BASED MEDICINE: PCI of culprit lesions (associated with reversible ischemia) makes sense and improves symptoms and sometimes also outcome PCI of non-ischemic lesions has no benefit, is not superior to medical treatment, potentially harmful, and unnecessary expensive FFR is the gold standard for assessment of ischemia in the catheterization lab DEFER study; JACC 2007 ACIP study; Circulation 1997 Courage trial; NEJM 2007 Let s measure FFR

During Maximal Vasodilatation P a 100 P v 0 Q P a 100 P d 70 P v 0 P FFR myo = P d P a = 0.70

AORTA 100 mmhg IVUS-CSA pressure (Pd) (mm Hg) 100 100 200 150 flow (Q) (ml/min) 9 mm 2 100 100 7 mm 2 100 75 5 mm 2 100 100 APEX 50 25 3 mm 2

Threshold value of FFR to detect significant stenosis FFR non-signif. stenosis significant 1.0 0.80 0.75 0 FFR is the only functional index which has ever been validated versus a true gold standard. (Prospective multi-testing Bayesian methodology) ALL studies ever performed in a wide variety of clinical & angiographic conditions, found threshold between 0.75 and 0.80 Sensitivity : 90% Specificity : 100% N Engl J Med 1996; 334:1703-1708

LCA RAO 30/20 view

verifying equal pressures before entering the coronary artery

PW in LAD artery

resting adenosine pull-back LAD artery

resting adenosine LCX

LCX Pull-back & Advance

LCX after stenting (Endeavour 3.5 x 12)

resting adenosine LCX after stenting

RCA

verifying equal pressures before entering RCA

Pressure Wire in RCA

hyperemic pull-back recording RCA distal stenosis proximal stenosis

LESSONS FROM THIS PATIENT: only 1 stent necessary ; cost-savings of Euro 3300,- if treatment was based upon angio and performed by more agresssive interventionalist (or had been randomized to angio-guided arm of FAME study), at least 3 and maybe 4 or 5 stents would have been placed, which would have increased risk and would have been unnecessary expensive ANGIO-GUIDED MULTIVESSEL PCI versus FFR-GUIDED (= ischemia-guided) MULTIVESSEL PCI What is better? FAME study has to answer the question decisively (FFR-guided ~ better, cheaper, quicker )

FFR-guided Angio-guided FFR-guided vs. Angio-guided multivessel PCI (125 patients) (event-free survival after 30 months) Leesar et al, JACC 2005

FAME FAME STUDY Functional vs Angiographic Multivessel Evaluation Prospective and randomized multicenter trial in 1000 patients undergoing multivessel PCI angio-guided: all lesions > 50% DES-stented FFR-guided: DES-stents in lesions with FFR < 0.80 Endpoints: outcome, symptoms, cost-efficiency 20 centers in USA and Europe Inclusion has been completed now Follow-up completed at TCT 2008

Flow Chart Informed consent Patient with MVD Indicate all stenoses > 50% by eyeballing Randomization Exclusion criteria: LM disease Previous CABG MI<5 days, unless Cardiogenic shock Pregnancy Life expectancy less than 2 years FFR-guided Angio-guided FFR measured in all arteries. Stent only stenoses with FFR 0.80 by DES - stent Stent all indicated stenoses by DES-stent anyway Plavix 12 months Follow up Plavix 12 months

FAME FAME STUDY Functional vs Angiographic Multivessel Evaluation Prospective and randomized multicenter trial in 1000 patients undergoing multivessel PCI Hypothesis: FFR-guided multivessel PCI is superior to angio-guided multivessel PCI FOLLOW-UP WILL BE COMPLETED ON SEPTEMBER 27th COMPLETE RESULTS AT TCT 2008

FAME: Preliminary baseline data Europe (1) ~ 60% of all screened patients were included!!! Age (yrs) Male FFR-group (n=368) 66 74% Angio-group (n=352) 64 70% CCS Class 2,4 2,4 Diabetes 20% 23% LV ejection fraction 57% 58% Ischemia detected 40% 42%

FAME: Preliminary baseline data - Europe Acute chest pain with EKG FFR-group (n=368) 14% Angio-group (n=352) 19% Acute chest pain no EKG Previous PCI 12% 27% 12% 24% Previous MI 35% 35% Lesions indicated 2,8 2,7 Stents per patient 1,9 2,9

FAME: Preliminary baseline data - Europe FFR-group Angio-group (n=368) (n=352) QCA: Stenosis % 58,8 56,3 QCA: Ref. diameter (mm) 2,46 2,41 Procedure time (min) 67 66 NS Contrast agent used (ml) 263 293 P<0.01

FFR IN MULTIVESSEL DISEASE SUMMARY Coronary pressure measurement is a helpful, easy, and relatively cheap tool in multivessel disease to: select the culprit spots and segments out of the many abnormalities which are often present discrimate if PCI of a particular spot or segment makes sense evaluate the result of stenting with prognostic implications and to avoid additional interventions which increase risk without benefit for the patient

Complete vs Incomplete Revascularization: What was wrong the wrong concept in the (mostly retrospective) studies performed so far?! e.g. ARTS-studies: 30% incomplete revascularization, but. arbitrary choice of no revascularization, or even worse: no revascularization because of technical difficulties considerable number of the non-revascularized lesions were ischemic lesions Whereas among the treated lesions, quite a bit of non-ischemic lesions must have been stented

Does routine measurement of FFR influence our strategy in MVD?? Study by Dr F. Mendes, Cabo Frio, Brasil all consecutive patients with MVD during 3 months (september december 2004): 195 patients revascularization strategy based upon angio assessed by 3 operators FFR measured in all stenoses and used for final decision making change in strategy in 34% of lesions and 45 % of patients F. Mendes SantÁna, JACC 2006

Clinical Outcome According to the Compliance with FFR 409 patients + FFR measurements Clinical outcome at one year MACE Rate at 1 y (%) 18 16 14 12 10 8 6 4 2 0 FFR<0.80 Revasc FFR>0.80 No Revasc FFR>0.80 Revasc FFR<0.80 No Revasc FFR Compliant FFR NON Compliant Legalery et al Eur Heart J 2005

Clinical Outcome According to the Compliance with FFR 409 patients + FFR measurements Clinical outcome at one year Legalery et al Eur Heart J 2005 MACE Rate at 1 y (%) 18 16 14 12 10 8 6 4 2 0 FFR<0.80 Revasc FFR>0.80 No Revasc FFR>0.80 Revasc FFR<0.80 No Revasc FFR Compliant FFR NON Compliant FFR < 0.80 : PCI results in 3 x lower event rate FFR > 0.80 : PCI results in 3 x higher event rate

COURAGE TRIAL: SOME CRITICAL NOTES How representative is the Courage Trial? only 6% of eligible patients were truly included Two-way negative bias for PCI group: 1. In PCI group, selection of lesions to be stented was on the basis of angiography at least 30% unnecessary stents, which unfavourably affects prognosis 2. In PCI group, also a number of ischemic lesions must have been missed, which also unfavouraby affects prognosis ( ACIP-trial, Circulation 1996) In terms of functional class the PCI group did better than the medical group, particularly in patients with proven ischemia!